Although phosphate salts have been advocated in the therapy of diabetic ketoacidosis (DKA) for many years, few centers use this routinely. Hypophosphatemia and a concomitant fall in red cell 2,3-diphosphoglyceric acid (2,3-DPG) have long been recognized to accompany DKA, and this is known to have an effect on oxyhemoglobin dissociation and to potentially produce tissue hypoxia. The present study attempts to demonstrate the effect of phosphate therapy in DKA patients in a randomized prospective protocol. Two groups of patients are being studied, one with and the other without phosphate therapy. All other treatment modalities including insulin, total amount fluid replacement, potassium, and other supportive care are maintained constant for both groups. Measurements of serum phosphate, erythrocyte 2,3-DPG, ATP, electrolytes, calcium and ionized calcium are measured serially during the course of treatment. Initial studies indicate that phosphate therapy can maintain serum phosphate within the normal range and begin to elevate erythrocyte 2,3-DPG within the first 24 hours. Studies to validate these observations in a larger population are ongoing.